Caffeic acid phenethyl ester attenuates neuropathic pain by suppressing the p38/NF-κB signal pathway in microglia

BACKGROUND: Management of neuropathic pain is still a clinical challenge. Evidence has accumulated indicating that propolis is effective in attenuating neuropathic pain; however, the mechanism is not fully understood. Our present study investigated the effects and the possible mechanism of caffeic acid phenethyl ester (CAPE), the main ingredient of propolis, in improving neuropathic pain via its inhibition on p38/NF-κB signal pathway in microglia. MATERIALS AND METHODS: Chronic constriction injury (CCI) mice model and the microglial cell line BV-2 were used to investigate the effects and the mechanism of CAPE. Cell signaling was measured by real-time PCR, Western blotting and immunofluorescence assay. RESULTS: CAPE relieved neuropathic pain behaviors induced by CCI in mice. CAPE also inhibited CCI-induced activation of microglia. Furthermore, CAPE suppressed the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of NF-κB and decreased the expression of proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6. CONCLUSION: CAPE was found to be an effective and safe drug candidate for alleviating neuropathic pain by its powerful inhibition on the P38/NF-κB signal pathway.